Basic Sciences Differential Susceptibility to Axonopathy in Necrotic and Non-Necrotic Perinatal White Matter Injury

نویسندگان

  • Art Riddle
  • Kevin X. Chen
  • Christopher D. Kroenke
چکیده

Background and Purpose—White matter injury (WMI) is the leading cause of brain injury in preterm survivors and results in myelination failure. Although axonal degeneration occurs in necrotic lesions, the role of axonopathy in myelination failure remains controversial for diffuse non-necrotic WMI, which is currently the major form of WMI. We determined the burden of axonopathy in diffuse lesions. Methods—We analyzed WMI in a preterm fetal sheep model of global cerebral ischemia that replicates the relative burden of necrotic and non-necrotic human WMI. WMI was analyzed at 1 or 2 weeks after ischemia and identified by ex vivo high-field (11.7 Tesla) magnetic resonance imaging of fixed brain tissue. Axonal integrity was analyzed by immunohistochemical detection of axon injury markers and by transmission electron microscopy to quantify axon loss and degeneration in magnetic resonance imaging-defined lesions. Results—Axonal degeneration, defined by staining for neurofilament protein and -amyloid precursor protein, was restricted to discrete necrotic foci with robust microglial activation. Unexpectedly, axonal degeneration was not visualized in the major form of WMI, which comprised large non-necrotic lesions with diffuse reactive astrogliosis. In these major lesions, quantitative electron microscopy studies confirmed no significant differences in the density of intact and degenerating axons or in the distribution of axon diameters relative to controls. Conclusions—The mechanism of myelination failure differs significantly in perinatal WMI dependent on the burden of necrosis. Axonopathy is associated with focal necrotic injury but not with primary diffuse non-necrotic lesions, which supports that intact axons in the primary lesions are potential targets for myelination. (Stroke. 2012;43:178-184.)

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Differential susceptibility to axonopathy in necrotic and non-necrotic perinatal white matter injury.

BACKGROUND AND PURPOSE White matter injury (WMI) is the leading cause of brain injury in preterm survivors and results in myelination failure. Although axonal degeneration occurs in necrotic lesions, the role of axonopathy in myelination failure remains controversial for diffuse non-necrotic WMI, which is currently the major form of WMI. We determined the burden of axonopathy in diffuse lesions...

متن کامل

Novel Approach of Differential Staining to Detect Necrotic Cells in Preimplantation Embryos

Background This novel approach describes a rapid and simple method for identification of necrotic vs. viable cells within a mammalian blastocyst. MaterialsAndMethods Hatched bovine blastocysts produced in vitro were first incubated for 30 min in pre-equilibrated culture medium containing propidium iodide (PI; 300μg/ml) and bisbenzimide (Hoechst: H33342; 5μg/ml) fluorescent dyes. Embryos were th...

متن کامل

Isolation, identification, and antimicrobial susceptibility of Clostridium perfringens isolates from acute necrotic enteritis of broiler chickens

The aim of this study was to isolate, identify and determine the antimicrobial susceptibility of Clostridium perfringens (CP) isolates from acute necrotic enteritis of broiler chickens. All broiler carcasses diagnosed as necrotic enteritis (NE) were sampled, subjected to microbial tests and 40 isolates were identified according to standard procedures. The antimicrobial susceptibility of CP isol...

متن کامل

Maturation-dependent vulnerability of perinatal white matter in premature birth.

Survivors of premature birth have a predilection for perinatal brain injury, especially to periventricular cerebral white matter. Periventricular white matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia) and ...

متن کامل

An unusual necrotic myositis by Clostridium perfringens in a German Shepherd dog: A clinical report, bacteriological and molecular identification

Clostridial myositis, considered to be rare in pet animals, is an acutely fatal toxaemic condition. Some species of clostridia are responsible for necrotic myositis. A 2-year-old male German shepherd dog was admitted with non-weight bearing lameness and massive swelling of the left hind limb. Clostridium perfringens type A with alpha toxin was diagnosed as a pathogenic agent. Based on ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2011